Angiogenesis is a highly complex and ordered process whereby new blood vessels are formed from preexisting blood vessels. Angiogenesis is critically important for the development and maintenance of normal tissues, and for the progression of many human diseases including cancer. Because angiogenesis is required to support advanced progression of many diseases, it is thought that halting angiogenesis holds potential for minimizing disease progression. TGF-B is believed to be a powerful regulator of normal and abnormal angiogenesis, but the molecular mechanisms by which TGF-B regulates angiogenesis are largely unknown. The experiments in this proposal are designed to test the hypothesis that TGF-B signaling regulates the expression of genes required for proper blood vessel formation, and that these genes in turn regulate key steps in new blood vessel formation. In testing this hypothesis, we aim to (1) discover novel genes involved in the process of angiogenesis; (2) discover novel TGF-B regulated genes involved in the process of angiogenesis; and (3) characterize identified genes based on their effects on essential steps for proper angiogenesis. In meeting these aims we will discover and characterize novel genes which are important for controlling angiogenesis and may therefore one day, be used as molecular targets for small molecules designed to slow or halt angiogenesis thus improving clinical outcomes for cancer patients.